It is well known that increasing an individual's exercise endurance can ameliorate multiple disease processes. We have identified possible quantitative trait loci (QTL) on Chromosomes 2, 8,13, and X that appear to be involved in the genetic regulation of maximal exercise endurance. Therefore, the overall objective of this proposal is to determine the specific genes involved in the control of inherent exercise endurance. This objective will be fulfilled through the following Specific Aims: 1) To complete a genetic linkage analysis and generate high-resolution linkage maps of the high exercise endurance (HEE = Balb/cJ) and low exercise endurance (LEE = DBA/2J) phenotypes;2) To examine the mechanisms that confer differential maximal exercise endurance phenotypes, we will develop congenic strains of mice that contain the candidate regions from Specific Aim 1;3) To characterize the maximal exercise endurance, central physiological response, and peripheral physiological response in congenic, HEE, and LEE parental mouse strains;and 4) To characterize and compare the gene expression of the congenic, HEE, and LEE parental mouse strains. The Specific Aims, when fulfilled, will be significant given the health risk of hypokinetic diseases. Understanding the genetic factors that predispose an individual to a certain fitness level could lead to better methods of improving the physical health and well-being of individuals. Unlike other past attempts, this project is unique in that we are proposing to use common, but powerful, genetic research techniques to investigate this area. This will be the first project investigating the genetic basis of exercise endurance to use these techniques that have already proven successful in other fields.